Genetic Variant SRRM3:p.Ser80Leu (chr7-76248193-C-T) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001110199.3(SRRM3):c.239C>T(p.Ser80Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000026 in 1,612,554 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000085 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000020 ( 0 hom. )

Consequence

SRRM3
NM_001110199.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.48

Variant links:

Genes affected

SRRM3 (HGNC:26729): (serine/arginine repetitive matrix 3) Predicted to enable mRNA binding activity. [provided by Alliance of Genome Resources, Apr 2022]

SRRM3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.042861372).

BS2

High AC in GnomAd4 at 13 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SRRM3	NM_001110199.3 link	c.239C>T	p.Ser80Leu	missense_variant	Exon 3 of 15	ENST00000611745.2	NP_001103669.1	A0A087WXA3
SRRM3	NM_001291831.2 link	c.239C>T	p.Ser80Leu	missense_variant	Exon 3 of 16		NP_001278760.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SRRM3	ENST00000611745.2 link	c.239C>T	p.Ser80Leu	missense_variant	Exon 3 of 15	5	NM_001110199.3	ENSP00000480851.1		A0A087WXA3
SRRM3	ENST00000479294.2 link	n.324C>T		non_coding_transcript_exon_variant	Exon 2 of 3	2

Frequencies

GnomAD3 genomes

AF:

0.0000854

AC:

AN:

152158

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000314

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000366

AC:

AN:

245848

Hom.:

AF XY:

0.0000224

AC XY:

AN XY:

133784

show subpopulations

Gnomad AFR exome

AF:

0.000528

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000559

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000199

AC:

AN:

1460278

Hom.:

Cov.:

AF XY:

0.0000220

AC XY:

AN XY:

726264

show subpopulations

Gnomad4 AFR exome

AF:

0.000777

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.00e-7

Gnomad4 OTH exome

AF:

0.0000332

GnomAD4 genome

AF:

0.0000854

AC:

AN:

152276

Hom.:

Cov.:

AF XY:

0.0000940

AC XY:

AN XY:

74452

show subpopulations

Gnomad4 AFR

AF:

0.000313

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000658

Hom.:

Bravo

AF:

0.000121

ESP6500AA

AF:

0.000638

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000581

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jun 21, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.239C>T (p.S80L) alteration is located in exon 3 (coding exon 2) of the SRRM3 gene. This alteration results from a C to T substitution at nucleotide position 239, causing the serine (S) at amino acid position 80 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.43

CADD

Uncertain

DANN

Pathogenic

1.0

Eigen

Benign

-0.11

Eigen_PC

Benign

-0.010

FATHMM_MKL

Benign

0.58

LIST_S2

Uncertain

0.89

M_CAP

Benign

0.013

MetaRNN

Benign

0.043

MetaSVM

Benign

-0.66

PrimateAI

Uncertain

0.52

Sift4G

Uncertain

0.0070

Vest4

0.29

MVP

0.043

ClinPred

0.094

GERP RS

4.2

gMVP

0.55

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over